title: [Mutation of isocitrate dehydrogenase 2 (IDH2) gene in Chinese AML patients and its clinical significance].
abstract: This study was purpose to analyze the frequency and of isocitrate dehydrogenase 2 (IDH2) gene mutation in acute myeloid leukemia (AML) and its clinic significance. The multiplex polymerase chain reaction (PCR) and sequencing were performed to screen 192 AML patients for exon 4 of the IDH2 gene. FLT3, NPM1, CEBPA, c-kit and WT1 mutations were also included in analysis. The results showed that IDH2 mutation was found in 14 (7.29%) of 192 patients. There were 9 AML patients with R140Q mutation, 1 patient with R140W mutation, and 1 patient with R172K mutation. IDH2 aberrations significantly more were detected in French-American-British (FAB) M5 (P < 0.005) than other types. There was no statistical difference in age, sex, WBC, platelet count, bone marrow blasts count, hemoglobin as compared with IDH2 wild-type. For immunotype analysis, IDH2 mutation patients were more likely to express CD34 and CD13, less CD36. IDH2 mutation combined with FLT3/ITD mutation was found in 7 cases, with CEBPA mutation in 4 cases, with NPM1 mutation in 4 cases, with Dnmt3a mutation in 5 cases, neither with c-kit, IDH1 or WT1 mutation for no one, which revealed a significant interaction between IDH2 mutation and the FLT3/ITD positive genotype, Dnmt3a mutated, and IDH1 wild-type. IDH2 mutation was detected in 5 (8.47%) of 59 CN-AML. There was no significant difference of IDH2 mutation incidence between the normal and abnormal karyotype. The CR rate was higher in IDH2 R140 mutated patients than wild-type ones, but there was no significant in the two group. It is concluded that the rate of IDH2 mutation is 7.29% in Chinese AML patients and 7.81% in CN-AML. IDH2 mutation is significantly associated with AML-M5, FLT3/ITD, Dnmt3a, IDH1 wild-type and fusion gene wild-type, but not with age, leucocyte and platelet counts in peripheral blood, karyotype, NPM1, CEBPA, c-kit or WT1 mutation. And IDH2 R140 mutation has no impact on CR rate.
authors.affiliation: Department of Hematology, Huazhong University of Science and Technology, Hubei Province, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Shang
authors.forename: Di
authors.initials: D
authors.lastname: Wang
authors.forename: Ming
authors.initials: M
authors.lastname: Xiao
authors.forename: Jue
authors.initials: J
authors.lastname: Wang
authors.forename: Tong-Juan
authors.initials: TJ
authors.lastname: Li
authors.forename: Yue-Chao
authors.initials: YC
authors.lastname: Zhao
authors.forename: Chun-Rui
authors.initials: CR
authors.lastname: Li
authors.forename: Jian-Feng
authors.initials: JF
authors.lastname: Zhou
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics; D000090205:DNA Methyltransferase 3A; D005260:Female; D005838:Genotype; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D000090243:Nucleophosmin; D011379:Prognosis; D012074:Remission Induction; D025721:WT1 Proteins / Q000235:genetics; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
chemical_list: C000717967:DNMT3A protein, human; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D025721:WT1 Proteins; C583751:WT1 protein, human; D000090243:Nucleophosmin; C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3